Substituted nitrosopyrroles and method of preparing the same



United States Patent 2,805,227 Patented Sept. 3, 1957 lice SUBSTITUTEDNITROSOPYRROLES AND METHOD OF PREPARING THE SAME No Drawing. ApplicationJanuary 18, 1956, Serial No. 559,775

6 Claims. (Cl. 260-4263) This invention relates to substitutedalkylnitrosopyr- The present compounds can be used as fungicides insolution. They can also be mixed with solid carriers such as talc,kieselguhr, chalk, diatomaceous earth and the like and used as a dustingpowder. When using these compounds in solution, it may be desirable toalso use surface-active agents such as salts of alkyl and alkylarylsulfonates, alkyl sulfates, fatty acid ester of polyhydric alcohols suchas Span, the ethylene oxide addition prodnets of such as esters, as, forexample, Tween.

The following examples illustrate the preparation of compounds of thepresent invention:

EXAMPLE 1 T o a solution of 1114 parts by volume of concentratedsulfuric acid and 476 parts by volume of water, cooled rolecarboxylatesand method of preparing the same. to is added 1543 parts by Weight ofethyl 1,3,5

In the past mnloslipyrroles have been described;trirnethyl-Lpyrrolecarboxylate. After allowing to stir they i rare lnone have been one hour to complete solution, at 5-l0 C. is added Scnbedas havmg fungicidal actmty' gradually a solution of 70.3 parts by weightof sodium has been {Guild that limmsopyrriflfas havmg the 20 nitrite in132 parts by volume of water. The tempera- 10W mg Structure highly acnveas funglcldes: ture is maintained at 5l0 C. and the addition requiresO=N R1 30 to 40 minutes. The reaction mixture after an additional hourat 10 C. is poured on 6,350 parts by volume R2 of an ice-water mixture.The precipitated product is f filtered and washed with water. The crudeproduct,

R which weighs 118 parts, is dissolved by warming to 50 in which R is alower alkyl radical and R1 and R: are in 1950 Parts by Volume ofalcohol- Addition of members of the group consisting of lower alkyl andcar- 2500 Parts y VQlume of Walt" Causes the P f material bloweralkoxyradicals, one of which is a lower alkyl to separate as green ry which.when isolated y radical and the other a carbloweralkoxy radical. The Rfiltration and dried, 8 P i y weight- The groups may be different.product is ethyl l,3,5-trimethyl-4-nitrose-2-pyrrolecar- The compoundsof the present invention are light green boxylate, melmlg at to whitecrystalline solids. They are somewhat soluble EXAMPLE 2 in alcohol orchloroform and relatively insoluble in water.

The present compounds are prepared by reacting the 150 parts of diethyl3,5-dimethyl-2,4-pyrroledicarappropriate substituted pyrrole having afree hydrogen boxylate, 2250 parts by volume of dry toluene and 21.8 inthe 4-position with nitrous acid which may be formed parts of sodium areheated to 8085 C. in the presence in situ by the use of an alkali metalnitrite under aqueous of 6 parts by volume of ethanol for 4% hours.Addiacid condition. This reaction is generally carried out tion of 94.6parts by volume of diethyl sulfate is carried at a temperature of from 0to 30 C. Following com- 40 out. The mixture is heated for eleven hours.The inpletion of the reaction, the desired product is isolated solublesare filtered out and the filtrate is freed of toluene from the reactionmixture by dilution with an ice-water by distillation and steamstripping. The oil-in-water mixmixture. If desired purification isaccomplished by crysture solidified and the solid isolated isrecrystallized sevtallization from a suitable solvent such as alcohol,acetone, eral times from dilute alcohol to give 65 parts of l-ethyletc.3,5-dimethyl-2,4-pyrroledicarboxylate, melting point 38.5-

The starting materials for the process of the present 40.541.3 C.invention can be methyl, ethyl, propyl or butyl 1,3,5-t1'i- 64 parts ofdiethyl l-ethyl-3,5-dimethyl-2,4-pyrroledimethyl-Z-pyrrolecarboxylate;methyl, ethyl, propyl or carboxylate is dissolved in 216.5 parts byvolume of conbutyl 3,5-dimethyl-l-lower alkyl-2-pyrrolecarboxylate;centrated sulfuric acid while maintaining the temperarnethyl, ethyl,propyl or butyl l,2,S-trimethyl-B-pyrroleture at 30 C. After allowing tostand at 30 C. for carboxylate and the like. one hour more, the solutionis poured in 1500 parts by The compounds of the present invention areactive volume of ice and water. The solid, which is filtered against anumber of fungi as shown in the following table: and washed with water,is slurried in 1080 parts by vol- TABLE Antifungal activity [Minimalinhibitory concentrations in mg. per ml.]

Compound C. a. S. c. M. r. F. e. H. c. I T. m.

0.06 0.06 3 0. 25 f; 0.06 Ethyl 1,3,5-trimethyl-4-nltroso-2- (1064ppyrrolecarboxylate 0. 00s 0. 015 0.015 0. 0a M15 0.06 Ethyl3,5-d1methyl-lethyl+nltroso- 2-pyrrolecarboxylate 0.06 0.015 0.03 0.120.12 0.25

C. a.-Ctmdida albicans.

S. c.Sat-charomyces carlsbememz's. M. r.Mucor ramanniamts.

F. e.Fu-sarium epispharia.

H. c.-Hormodmdmm cladoaporoidea. 7. m.Trlchophpmn mentagraphytes.

me of water and 108 parts by volume of 5 N sodium hydroxide. Afterstirring for some time, a little unreacted material i filtered out andthe clear solution is acidified. The precipitate is isolated and weighs45.5 parts, melting at 158159.3 C. (dec.), and analyzed for 5carbethoxy-l-ethyl-2,4-dimethyl 3 pyrrolecarboxylic acid.

45 parts of S-carbethoxy-1-ethyl-2,4-dimethyl-3-pyrrolecarboxylic acidis heated in 108 parts by volume of dry glycerine at l90200 C. for twohours. The cool solution is extracted with ether, water added andextracted thrice more with ether. The combined ether layers are washedwith water, desiccated, and freed of ether by distillation. The residuedistills at 73.577 C. at 0.45 mm. to give 28.5 parts ofethyl-1-ethyl-3,5-dimethy1-2-pyrrolecarboxylate.

In a solution of 11.14 parts by volume of concentrated sulfuric acid and4.8 parts by volume of water is dissolved at 5-8 C. 14.25 parts ofethyl-1-ethyl-3,5-dimethyl-2-pyrrolecarboxylate. To this solution at 510C. is added gradually 1.53 parts of sodium nitrite in 9 parts by volumeof water. After standing 20 minutes, the solution is poured over 480parts by volume of ice and water. The green oil is extracted out thricewith ether and desiccated. Removal of the ether under reduced pressuregives a dark emerald-green oil which crystallizes beautifully below 5'C. as ethyl-1-ethyl-3,5-dimethyl-4-nitroso-2-pyrrolecarboxylate.

EXAMPLE 3 Ethyl 1.2,5-trimethyl-3-pyrrolecarboxylate (22 parts) wasdissolved in a mixture of glacial acetic acid (300 parts) and water (100parts) and cooled to -5 C. Sodium nitrite (10 parts) was dissolved inwater (50 parts) and cooled at 0 C. The solutions were combined and heldat 4 C. for one hour. Pouring into 2000 parts of ice water gave aprecipitate of ethyl 1,2,5-trimethyl-4-nitroso-3-pyrrolecarboxylate,which was collected and dried. It was purified by solution in 200 partsof acetone and subsequent reprecipitation by 4000 parts of water. Theyield of purified product, ethyl 1,2,5-trimethyl-4-nitroso-3-pyrrolecarboxylate, was 8 parts, decomposing at109-110 C.

I claim:

1. A compound of the group having the general formula O ==N R1 11 U: R)i.

References Cited in the file of this patent UNITED STATES PATENTS RogersAug. 14, 1945 Goodings et a1 Nov. 5, 1946 OTHER REFERENCES Angeli etal.: Beilstein (Handbuch, 4th ed.), vol. 21, p.273 (1935).

1. A COMPOUND OF THE GROUP HAVING THE GENERAL FORMULA: